Figure 5

Pathways concerned with the regulation of glycolysis and the effects of HIF-1 deficiency in Hepa-1 tumours. In the wild-type tumours (WT), [ATP] would tend to inhibit PFK activity. However in HIF-1 deficiency (c4), enzymes in the glycolytic pathway are down-regulated to 42-74% of the WT protein expression and the resulting decrease in [ATP] causes an increase in [AMP] (due to the adenylate kinase equilibrium). AMP acts as an allosteric activator of PFK, and the ATP/AMP ratio in c4 tumours doubles the PFK catalytic activity (see Figure 4), allowing glycolytic flux through the pathway (glucose to lactate) to be maintained at WT levels.